1. Field of the Invention
This invention pertains to a method and apparatus for diagnosis and treatment of pathologic sites within a blood vessel. More particularly, this invention pertains to such method and apparatus for diagnosis and treatment of vulnerable plaque.
2. Description of the Prior Art
The formation of plaque within blood vessels has long been recognized as a serious disease requiring medical intervention. Commonly, the focus of medical intervention has been on so called “stenotic” plaque. Stenotic plaque is commonly characterized as a stable plaque in the form of a thick fibrous cap. The plaque may occlude a blood vessel by 50% or more.
At about 50% stenosis (i.e., 50% occlusion of a blood vessel,) such plaque is symptomatic in that the patient experiences chest pain (referred to as angina). Treatment of such plaque typically occurs when the blood vessel is occluded by 70% or more.
The identification of stenotic plaque is readily determined and visualized through standard procedures such as IVUS (intravascular ultrasound), angiography or fluoroscopy. Once the location of a stenotic plaque is identified, the plaque may be treated through any one of a number of treatment modalities including angioplasty, placement of a stent, or coronary bypass surgery. Recently, the introduction of drug-eluting stents have been used for the treatment of such plaque.
Unfortunately, an additional category of plaque has historically evaded detection and treatment. This second category of plaque is referred to as vulnerable plaque which appears to be caused by an inflammatory response to unacceptable levels of pathologic compounds in the vessel wall—such materials include cholesterol and other lipids and the like.
Vulnerable plaque is believed to be responsible for as much as 85% of heart attacks. Vulnerable plaque has been defined as a plaque which is often not stenotic and has the likelihood of becoming disruptive and forming a thrombogenic focus.
Unlike stable plaque, vulnerable plaque is commonly associated with a pool of lipid material separated from a blood vessel by a thin fibrous cap. Typically, vulnerable plaque does not protrude into the blood vessel by more than 50%. However, when the thin fibrous cap exposes the lipid through either rupture or erosion, the lipid can instigate rapid thrombus formation within the blood vessel leading to infarction or stroke. When the plaque ruptures there is contact between the blood, the lipid core and other plaque compounds that appears to instigate the majority of coronary thrombi.
Since the vulnerable plaque does not protrude as significantly within the blood vessel as stenotic plaque, such vulnerable plaque is often not identifiable through traditional visualization technique such as angiography. Also, a patient typically has no symptoms prior to heart attack. Therefore, vulnerable plaque presents a significant diagnostic problem. A significant diagnostic issue is presented in attempting to determine who is prone to vulnerable plaque, identifying the plaques and localizing plaques that are of high vulnerability and capable of causing a catastrophic event.
Certain primary disease markers are believed to help identify the existence of vulnerable plaque in a patient's vasculature. For example, C-reactive protein (CRP) is a promising primary marker for vulnerable plaque.
Elevated cholesterol levels, specifically LDL levels, have long been one of the key risk factors used to identify a risk for coronary artery disease. However, recent research has centered on the validity of C-reactive protein as a key heart disease marker.
CRP is a protein most commonly associated with inflammation. CRP levels rise as the amount of inflammation in the body rises. CRP has been shown to be localized at the point of inflammation and to be systemic and disbursed throughout the body. CRP is of interest to clinicians and so may be a primary marker for predicting the existence of vulnerable plaque, which is an inflammatory response.
In addition to CRP, other primary markers are T-wave alternans and calcium deposition determined by radiographic temography or MRI. CRP is a biomarker produced in the liver in response to multiple inflammatory, infectious and immunological challenges. It is also believed that temperature differentials are a possible way to localize vulnerable plaques. Other techniques for identifying plaque include optical coherence tomography (OCT) and thermography. OCT measures a difference in an index of refraction between fibrous tissue and macrophage-laden tissue. OCT is limited by depth of penetration (2 mm) and clinician interpretation of the image. Thermography relies on temperature differentials of 0.1-0.2° C. higher than non-diseased vasculature as a predictor of vulnerable plaque. The thermistors need good contact with the lesion which leads to concerns that the device itself may cause plaque to rupture.
While CRP is a promising marker, it is previously believed to be used only as a general screening technique since it is typically identified as a systemic response not adequate to localize and identify a specific plaque.
Another example of a marker is a change in acidity (i.e., pH) of the blood near a vulnerable plaque. The pH of the inflamed vulnerable plaque can be as low as 6.3 versus a normal blood pH of 7.4. This change in pH affects the local environment as well (e.g., changes in blood pH permitting indirect detection of pH in the inflammatory site).
It is an object of the present invention to provide a method and apparatus for diagnosing and localizing vulnerable plaque or other pathologic site.